β-Triketone Nitisinone Kills Insecticide-Resistant Mosquitoes via Skin Absorption | Parasites and Vectors

       Insecticide resistance among arthropods that transmit diseases of agricultural, veterinary and public health importance poses a serious threat to global vector control programmes. Previous studies have shown that blood-sucking arthropod vectors experience high mortality rates when ingesting blood containing inhibitors of 4-hydroxyphenylpyruvate dioxygenase (HPPD), the second enzyme in tyrosine metabolism. This study examined the efficacy of β-triketone HPPD inhibitors against susceptible and pyrethroid-resistant strains of three major disease vectors, including mosquitoes transmitting historical diseases such as malaria, recurrent infections such as dengue and Zika, and emerging viruses such as Oropuche and Usutu viruses.

       Differences between topical, tarsal and vial application methods, application methods, insecticide delivery and duration of action.
       However, despite the difference in mortality between New Orleans and Muheza at the highest dose, all other concentrations were more effective in New Orleans (susceptible) than in Muheza (resistant) over 24 hours.
       Our results show that nitisinone kills blood-sucking mosquitoes via transtarsal contact, whereas mesotrione, sulfotrione, and tepoxiton do not. This killing method does not discriminate between mosquito strains sensitive or highly resistant to other classes of insecticides, including pyrethroids, organochlorines, and possibly carbamates. Furthermore, the efficacy of nitisinone in killing mosquitoes via epidermal absorption is not limited to Anopheles species, as demonstrated by its efficacy against Strongyloides quinquefasciatus and Aedes aegypti. Our data support the need for further research to optimize nitisinone absorption, possibly through chemical enhancement of epidermal absorption or the addition of adjuvants. Through its novel mechanism of action, nitisinone exploits the blood-sucking behavior of female mosquitoes. This makes it a promising candidate for innovative indoor residual sprays and long-lasting insecticidal nets, especially in regions where traditional mosquito control methods are ineffective due to the rapid emergence of pyrethroid resistance.